Cardiovascular disease (CVD), including coronary heart disease, atherosclerosis, stroke, myocardial infarction, sudden death syndrome, is the number one cause of death in most developed countries all over the world. Also, in developing countries, the prevalence of CVD is on the increase and appears to be linked to people adopting a more Westernized (North American) diet (high fat) and lifestyle (sedentary). Elevated circulating cholesterol levels, in particular low-density-lipoprotein cholesterol (LDL-cholesterol) levels, have been well established as one of the major risk factors for the development and progression of CVD. A high level of circulating triglycerides is also a critical risk factor in the increased incidence of CVD. Accordingly, reducing total cholesterol and/or triglyceride levels is advised to high risk patients to reduce cardiovascular-related risk factors that are known and demonstrated to be associated with a higher incidence of morbidity and mortality. Subjects with obesity, diabetes and hyperlipidemia are three major subgroups of the population that are adversely affected by high cholesterol and triglyceride levels.
To date, it is known that plant sterols/stanols and their various analogues can reduce circulating blood cholesterol concentration by inhibiting dietary and biliary cholesterol absorption in the intestine. Red Yeast Rice supplements lower blood cholesterol through inhibiting the activity of the rate-limiting enzyme, HMG-CoA reductase that essentially governs cholesterol biosynthesis in mammals. Berberine was most recently reported to be able to lower blood cholesterol through enhancing cholesterol clearance by increasing LDL-receptor mediated cholesterol clearance. These three types of bioactive compounds (berberine, plant sterols/stanols, and Red Yeast Rice) work through distinct mechanisms.
Presently available products have been demonstrated to work via different mechanisms and achieve the expected results to certain degree; however, the efficacy of presently available products is limited and/or is accompanied by side effects. Statin drugs reduce blood cholesterol through suppressing the activity of HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, but this class of compounds has little or no effect on lowering triglycerides. The major drawback of statin or statin-like compounds is that the synthesis of an important mitochondrial enzyme called Q10 is inhibited, depending on HMG-CoA reductase to be intact and functional. Blockage of HMG-CoA reductase by statins causes reduced coenzyme Q10 levels and this is thought to underlie the cause of a number of statin-associated muscle-related myopathies reported, such as muscle soreness, muscle weakness, muscle tenderness, intense muscle pain, peripheral neuropathy and muscle protein breakdown called rhabdomylosis and may underlie other side effects that are dependent on the presence of normal physiological levels of coenzyme Q10. In particular, rhabdomylosis can be both a serious and a life threatening side effect clearly associated with the use of statin drugs where the muscle breakdown causes major organ damage to both the liver and kidney that has resulted in many reported deaths. The all-cause discontinuation rate of statin use was about 10% and discontinuation because of adverse events was about 4%. Plant sterols and their different analogues inhibit cholesterol absorption and thus reduce cholesterol concentration in the plasma. However, when blood cholesterol concentration is reduced through the inhibition of cholesterol absorption, cholesterol synthesis increases simultaneously as a compensation mechanism to counteract the reduced absorption of dietary and biliary cholesterol. Plant sterols and their different analogues have not previously been shown to have any significant effect in reducing serum triglyceride levels.
A recent discovery of a botanical bioactive alkaloid compound berberine, contained in Chinese Huanglian, goldenseal, or goldthread, lowers cholesterol levels through increasing LDL-receptor mediated cholesterol clearance.